Despite optimal use of the several antiepileptic drugs marketed in the United States, many patients with epilepsy fail to experience seizure control and others do so only at the expense of significant toxic side effects. In the early 1970's, no convincing evidence had been published that the primary antiepileptic drugs marketed in the United States at that time controlled the seizures of more than 50% or improved more than 75% of the patients with epilepsy. The availability and use of several additional drugs since that time has brought improved seizure control to many patients. Notwithstanding the beneficial effects of the current drugs, there is still a need for new antiepileptic drugs with more selective anticonvulsant effects and less toxicity. E. A. Swinyard, et al., Epilepsia, 19, 409 (1978).
Various substituted phenyl pyridinyl ureas have been described but none having anticonvulsant activity. For example, M. I. Bruce and J. A. Zwar in Proc. Roy. Soc. (London), Sec. B. 165 (999), 245-65 (1966) disclose many N-mono- and N,N'-disubstituted ureas having cytokinin activity. N-(3,4-dichlorophenyl)-N'-3- and 4-pyridinyl ureas show such activity whereas the corresponding 2,5-dichloro compounds were inactive. In general, the authors concluded that phenyl ring substitution enhanced activity with meta substituents providing highest activity and ortho substituents lowest activity.
German patent publication No. 2,928,485 also describes various ureas including N-(3-chloro-4-trifluoromethylphenyl)-N'-3- and 4-pyridinyl ureas as being useful for inhibiting lipid absorption.
French patent publication No. 2,155,856 teaches various 2-pyridinyl ureas including N-(3,4-dichlorophenyl)-N'-2-pyridinyl urea as having anti-inflammatory and analgesic activity.
The present invention relates to novel 2,6-disubstitutedphenyl 3- and 4-pyridinyl ureas having valuable anticonvulsant properties and are thus useful for treating epilepsy.